Vitamin D Deficiency
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Basics
This topic covers the commonly acquired vitamin D deficiency and not type II vitamin D–resistant rickets/type I pseudovitamin D–resistant rickets (both rare autosomal recessive disorders).
Description
- Vitamin D is a hormone and a vitamin.
- Cholecalciferol (D3) is synthesized in the skin by exposure to ultraviolet B (UV-B) radiation. Ergocalciferol (D2) and D3 are present in foods.
- D2 and D3 are hydroxylated in the liver to 25 vitamin D (calcidiol), the major circulating form.
- Calcidiol is further hydroxylated in the kidney to the active metabolite 1,25 vitamin D (calcitriol).
- Hypocalcemia stimulates parathyroid hormone (PTH) secretion, which prompts increased conversion of 25 vitamin D to 1,25 vitamin D.
- 1,25 vitamin D decreases renal calcium and phosphorus excretion, increases intestinal calcium and phosphorus absorption, and increases osteoclast activity. The net result is an increase in serum calcium.
Epidemiology
- A community cohort study of asymptomatic adolescents in Boston found 24% were deficient, with 5% severely deficient.
- A study of hospitalized patients in Massachusetts found 57% vitamin D–deficient (VDD).
- Women with history of osteoporosis/osteoporotic fracture have high prevalence of vitamin D deficiency.
- A cohort study in Arizona found >25% of adults were VDD; highest rates among African Americans and Hispanics
- A study of about 56,000 individuals across Europe found 13% to have vitamin D deficiency.
Pediatric Considerations
National Health and Nutrition Examination Survey (NHANES) data suggest 70% of children do not have sufficient 25-OH vitamin D serum levels (9% deficient and 61% insufficient); deficiency has been associated with an increase in BP and decrease in high-density lipoprotein (HDL) cholesterol.
Etiology and Pathophysiology
- Insufficient dietary intake of vitamin D and/or lack of UV-B exposure (in sunlight) results in low levels of vitamin D.
- This limits calcium absorption, causing excess PTH release.
- PTH stimulates osteoclast activity, which helps to normalize calcium and phosphorous but results in osteomalacia.
- Dietary deficiency
- Inadequate vitamin D intake
- Inadequate sunlight exposure
- Institutionalized/hospitalized patients
- Chronic illness: liver/kidney disease
- Malabsorptive states
Genetics
Vitamin D–dependent rickets type 1 occurs due to inactivating mutation of the 1α hydroxylase gene; as a result, calcidiol is not hydroxylated to calcitriol.
Risk Factors
- Inadequate sun exposure
- Female
- Dark skin
- Immigrant populations
- Low socioeconomic status
- Latitudes higher than 38 degrees
- Elderly
- Institutionalized
- Depression
- Medications (phenobarbital, phenytoin)
- Gastric bypass surgery/malabsorption syndromes
- Obesity
- Rates higher in black and Hispanic populations
General Prevention
- Adequate exposure to sunlight and dietary sources of vitamin D (plants, fish); many foods are fortified with vitamin D2 and D3.
- Recommended minimum daily requirement is 600 IU/day from age 1 to 70 years and 800 IU/day for those >70 years. Up to 4,000 IU/day is safe in healthy adults without risk of toxicity.
- For ages 51 to 70 years, minimally recommended supplementation is 800 IU/day to prevent nonvertebral fractures.
Pediatric Considerations
- The American Academy of Pediatrics recommends all breastfed babies receive 400 IU/day of vitamin D beginning “within the first few days of life.”
- 2016 Global Consensus Recommendations suggest all infants, regardless of feeding method, begin vitamin D 400 IU within a few days of birth (1).
- Mid-Gestational vitamin D deficiency doubled risk of Autism Spectrum Disorder in European cohort (2)
Pregnancy Considerations
Insufficient data to recommend routine screening of all pregnancies; only “at risk” should be screened; it is safe to take 1,000 to 2,000 IU/day during pregnancy (3)[B].
Commonly Associated Conditions
- Osteomalacia, osteoporosis
- Premenstrual syndrome
- Rickets
- Celiac disease
- Gastric bypass
- Chronic renal disease
- Bacterial vaginosis in pregnant women
- Hypertension
- Cohort study found that vitamin D deficiency is correlated with increased risk of all-cause mortality.
ALERT
Vitamin D deficiency is associated with risk of myocardial infarction (MI) and all-cause mortality (4)[A].
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Basics
This topic covers the commonly acquired vitamin D deficiency and not type II vitamin D–resistant rickets/type I pseudovitamin D–resistant rickets (both rare autosomal recessive disorders).
Description
- Vitamin D is a hormone and a vitamin.
- Cholecalciferol (D3) is synthesized in the skin by exposure to ultraviolet B (UV-B) radiation. Ergocalciferol (D2) and D3 are present in foods.
- D2 and D3 are hydroxylated in the liver to 25 vitamin D (calcidiol), the major circulating form.
- Calcidiol is further hydroxylated in the kidney to the active metabolite 1,25 vitamin D (calcitriol).
- Hypocalcemia stimulates parathyroid hormone (PTH) secretion, which prompts increased conversion of 25 vitamin D to 1,25 vitamin D.
- 1,25 vitamin D decreases renal calcium and phosphorus excretion, increases intestinal calcium and phosphorus absorption, and increases osteoclast activity. The net result is an increase in serum calcium.
Epidemiology
- A community cohort study of asymptomatic adolescents in Boston found 24% were deficient, with 5% severely deficient.
- A study of hospitalized patients in Massachusetts found 57% vitamin D–deficient (VDD).
- Women with history of osteoporosis/osteoporotic fracture have high prevalence of vitamin D deficiency.
- A cohort study in Arizona found >25% of adults were VDD; highest rates among African Americans and Hispanics
- A study of about 56,000 individuals across Europe found 13% to have vitamin D deficiency.
Pediatric Considerations
National Health and Nutrition Examination Survey (NHANES) data suggest 70% of children do not have sufficient 25-OH vitamin D serum levels (9% deficient and 61% insufficient); deficiency has been associated with an increase in BP and decrease in high-density lipoprotein (HDL) cholesterol.
Etiology and Pathophysiology
- Insufficient dietary intake of vitamin D and/or lack of UV-B exposure (in sunlight) results in low levels of vitamin D.
- This limits calcium absorption, causing excess PTH release.
- PTH stimulates osteoclast activity, which helps to normalize calcium and phosphorous but results in osteomalacia.
- Dietary deficiency
- Inadequate vitamin D intake
- Inadequate sunlight exposure
- Institutionalized/hospitalized patients
- Chronic illness: liver/kidney disease
- Malabsorptive states
Genetics
Vitamin D–dependent rickets type 1 occurs due to inactivating mutation of the 1α hydroxylase gene; as a result, calcidiol is not hydroxylated to calcitriol.
Risk Factors
- Inadequate sun exposure
- Female
- Dark skin
- Immigrant populations
- Low socioeconomic status
- Latitudes higher than 38 degrees
- Elderly
- Institutionalized
- Depression
- Medications (phenobarbital, phenytoin)
- Gastric bypass surgery/malabsorption syndromes
- Obesity
- Rates higher in black and Hispanic populations
General Prevention
- Adequate exposure to sunlight and dietary sources of vitamin D (plants, fish); many foods are fortified with vitamin D2 and D3.
- Recommended minimum daily requirement is 600 IU/day from age 1 to 70 years and 800 IU/day for those >70 years. Up to 4,000 IU/day is safe in healthy adults without risk of toxicity.
- For ages 51 to 70 years, minimally recommended supplementation is 800 IU/day to prevent nonvertebral fractures.
Pediatric Considerations
- The American Academy of Pediatrics recommends all breastfed babies receive 400 IU/day of vitamin D beginning “within the first few days of life.”
- 2016 Global Consensus Recommendations suggest all infants, regardless of feeding method, begin vitamin D 400 IU within a few days of birth (1).
- Mid-Gestational vitamin D deficiency doubled risk of Autism Spectrum Disorder in European cohort (2)
Pregnancy Considerations
Insufficient data to recommend routine screening of all pregnancies; only “at risk” should be screened; it is safe to take 1,000 to 2,000 IU/day during pregnancy (3)[B].
Commonly Associated Conditions
- Osteomalacia, osteoporosis
- Premenstrual syndrome
- Rickets
- Celiac disease
- Gastric bypass
- Chronic renal disease
- Bacterial vaginosis in pregnant women
- Hypertension
- Cohort study found that vitamin D deficiency is correlated with increased risk of all-cause mortality.
ALERT
Vitamin D deficiency is associated with risk of myocardial infarction (MI) and all-cause mortality (4)[A].
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